This invention relates to certain 5'-deoxy-5'-substituted adenosines which are useful as inhibitors of S-adenosylmethionine decarboxylase (AdoMet-DC).
In recent years, there has been considerable research carried out that relates to the polyamine biosynthetic pathway. The polyamines putrescine, spermidine and spermine are known to be required for normal cell growth and differentiation, and it has been shown that interference with polyamine metabolism can lead to therapeutic effects, e.g., antiviral, antiparasitic or anticancer effects. See "Recent advances in the biochemistry of polyamines in eukaryotes", Pegg, Biochem. J. (1986) Vol. 234, pps. 239-262 and "S-ADENOSYLMETHIONINE DECARBOXYLASE AS TARGET OF CHEMOTHERAPY", Janne et al (1985), Advances in Enzyme Regulation, Vol. 24, pps. 125-139, the disclosures of which are incorporated herein by reference.
Kolb et al, Liebigs Ann. Chem., (1985), pps. 1036-1040; Khomutov et al, Bioorg. Khim., (1983), Vol. 9, pps. 130-131; and Artamonova et al, Bioorg. Khim., (1986), Vol. 12, pps. 206-212 all disclose 5'-deoxy-5'-substituted adenosines. Kolb et al discloses such compounds having the structure: ##STR4## and the two latter articles disclose such compounds having the structure ##STR5## wherein n=2 or 4. The latter two articles note that their compounds are inhibitors of AdoMet-DC.